It has become increasingly clear in recent years that induction of apoptosis is of great importance for the success of radiation-and chemotherapy. However, many tumor cells acquire resistance to the induction of apoptosis by up-regulation of the apoptosis antagonists Bcl-2 and Bcl-XL. Thus, an important target for therapeutic intervention would be to inactivate or lower the cellular levels of Bcl-2 and Bcl-XL. We recently reported that the short chain fatty acid butyrate can lower the cellular level of Bcl-XL in human fibroblasts and human breast cancer cells. Furthermore, we showed that butyrate acting in synergy with radiation, UV light and cisplatin to induce apoptosis. The goal of this proposal is to explore whether butyrate may act in synergy with radiation, chemotherapy or hormone withdrawal to induce prostate cancer cells to undergo apoptosis. In specific aim #1 we will address whether butyrate may act in synergy with ionizing radiation to preferentially induce apoptosis in prostate cancer cells compared to normal prostate cells. Preliminary results suggest that the prostate cancer cell line PC-3 is affected by butyrate at concentrations about ten-fold than what affected normal human fibroblasts. In addition, we show that butyrate significantly reduces the cellular level of Bcl-XL in PC-3 cells. In specific aim #2 we will explore whether butyrate may act in synergy with chemotherapy agents to induce apoptosis in prostate cancer cancers. Finally, butyrate will in specific aim #3 be used in combination with hormone withdrawal to explore whether butyrate act in synergy with hormone withdrawal to induce prostate cells to undergo apoptosis. These studies will define whether butyrate may be use in combination with traditional anti-cancer protocols for the treatment of prostate cancer.